Fragment molecular orbital (FMO) method is one of the approximations for calculating electronic properties of huge molecules such as DNA and protein. The accuracy and computational cost of FMO calculations depend critically on the way of dividing a molecule into fragments. In this study, we investigated the electronic properties of four types of DNA models by using our developed density functional (DFT) method based on FMO. In the FMO-DFT calculations, we considered the two types of ways of division for fragmentation, i.e., divisions into DNA bases and base pairs. Through the comparison with the results by conventional DFT calculations, it was clarified that the FMO-DFT calculations with a base fragmentation as well as with a base-pair fragmentation have a comparable accuracy with that obtained by the conventional DFT method for the electronic properties of DNA.

Quinolone derivatives are antibiotics with a 1,4-dihydro-quinoline-3-carboxylic acid skeleton, which have been under development by many pharmaceutical companies. An aromatic nucleophilic substitution (SNAr) reaction is the key reaction for manufacturing the quinolone derivatives. Therefore, the ability to predict experimental yields for the SNAr reactions is very useful for developing synthetic pathways for these compounds. In the present study, we tried to predict reaction yields by using the GA-PLS method with values calculated from the Molecular Orbital (MO) calculations as explanatory variables. The present GA-PLS analysis also adopted such experimental parameters as dielectric constants of solvents and reaction temperatures. Although it was necessary to classify nucleophiles and quinolone derivatives according to their geometry, we succeeded in making models associating the experimental yields with the parameters shown above. The analyses by using energy levels corresponding to more than two orbitals near HOMO and LUMO produced better results than those only from the energy levels of HOMO and LUMO. The GA-PLS method extrapolated variables closely related to the reaction mechanism for making the models. However, the method also selected as parameters important explanatory variables such as energy levels of HOMO and LUMO and electron densities of products in order to obtain models with high R² values. These variables are unrelated to the SNAr mechanism and are dependant on classification of the reactants according to their geometry. The difference of selected parameters suggests a difference of the reaction mechanisms according to the combination of nucleophiles and quinolones, which contradicts the experimental findings that all reactions proceed according to the same mechanism, i.e., the SNAr mechanism. We then tried to classify the data by reaction conditions. As a result, we were able to make a model by the classification according to the isolation method, which was not dependent on the chemical structure. This shows the large influence exerted by the difference of isolation method by having the assumed yield as the target variable, and the difficulty of modeling. Therefore, it is possible to predict the reaction yield by using the parameters calculated from the MO calculations, and it became clear that the differences of isolation methods were responsible for the difficulty of making a unified model.

To elucidate the effect of cyclic AMP and cyclic GMP addition to the catabolite activator protein (CAP) on its complex structure, we investigated the stable structures of CAP dimer, CAP-cAMP and CAP-cGMP complexes by the molecular mechanics calculations using the AMBER Force Field. The cAMP addition is found to have rather large effect on the CAP dimer structure compared with that by the cGMP addition. This finding is qualitatively consistent with the experimental result that only cAMP has an effect on enhancing the affinity between CAP and DNA, while cGMP does not.

Synthesis route design systems have been practically used for more than ten years to create new synthesis routes of compounds. The number of routes diverges for multi-step syntheses as the systems usually offer several routes for each step. It is very difficult for experimental chemists to determine which is the best for the target compound in the created routes. On the other hand, quantum mechanical calculations including searches of transition states (TSs) are very effective to clarify possibility of synthesis routes, i.e., if there is the TS for a route, there is possibility to synthesize the target by using the route and vice versa. Therefore, we should be able to find useful synthesis routes without experiments by fusing computational chemistry which analyzes reaction mechanisms and information chemistry which creates synthesis routes. However, there are few studies concerning with the promising method. In the present study, we described the transition state data base (TSDB) which makes it possible to effectively use the synthesis route system for developing new synthesis routes of compounds.

Recently, as information technology continues to develop, data mining methods, which are techniques for obtaining useful and understandable information from large numbers of data, have become more important in the fields of medical and pharmaceutical sciences. Such methods are being adopted for studies involving large numbers of data, such as DNA microarray or epidemiological data. However, most data mining methods are unsuitable in these fields because validating attributes such as the risk factors of medications are not easy to validate using models. Since understanding the relationships between treatments and their effects is especially important in medical and pharmaceutical sciences, practitioners in these fields tend to avoid such unsuitable methods for data analyses, even when large volumes of data have to be analyzed. The decision tree is one of these methods. In this study, we propose a novel procedure which enables users to clarify the relationships between attributes and classification results by tree models using resampling methods. Our new procedure has a function to obtain information about the significance of the attributes for tree models. In addition, this method can extend the applicability of decision tree-like methods.

Some scams of disguising imported food as domestic have been recently reported in Japan. Concerning wakame seaweed, which is indispensable in the Japanese diet, the situations is also the same. Most people would not be willing to consume them, if they are from other production areas. Analytical methods for determining the production centers are now definitely needed and such methods should be sensitive to determine any disguising. We found the feasibility using Visible-Nearinfraraed spectroscopy and some chemical information processing methods. In this analysis, we found a clear classification between the China, Kashiwazaki and others because we drew 3-D score plots of the principal component analysis after the variable selection using classification trees.

We investigated the charge transfer through single- and double-strand DNAs by molecular dynamics (MD) and molecular orbital (MO) methods. The stable structures of DNAs in water solvent were obtained by MD calculations. The energy levels and distributions of frontier molecular orbitals related to charge transfer were analyzed in detail by the semiemprical MO method. Furthermore, from the energy levels, the transfer integrals for a hole and an electron between DNA bases were estimated. Finally, we obtained the current-voltage characteristics in single- and double-strand DNAs based on these results. The calculated results are qualitatively in agreement with the experimental results.

The electronic properties of bikunin, which is a reaction part of a chimeric protein inhibiting cancer metastasis, were investigated by semiempirical molecular orbital (MO) calculations. From the distributions of highest occupied MO (HOMO) and lowest unoccupied MO (LUMO), the chemically reactive part of bikunin was specified to be the experimentally proposed site. Furthermore, some amino acids existing around the reaction part in bikunin were mutated by other amino acid, and the effect of mutations on the HOMO and LUMO distributions was investigated in detail by the MO calculations. Based on these results, we predicted which amino acid in bikunin is important for the chemical reaction between bikunin and cancer.

As an efficient medicine for inhibiting cancer metastasis without a side effect, a chimeric protein including urokinase was developed. For the amino terminal fragment (ATF) of the urokinase, which is a receptor-binding site of this chimeric protein, we investigated its stable structures by the AMBER force field. Their electronic properties were also investigated by semiempirical molecular orbital (MO) method. From the obtained energy levels and distributions of HOMO (highest occupied MO) and LUMO (lowest unoccupied MO), we found that the 30th Trp and the Cys-Cys bridge of the 13th-31st amino acids of ATF are related with the chemical reactivity of ATF. Furthermore, the effect of amino-acid mutations on the chemical reactivity of ATF was evaluated by the semiempirical MO method.

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Edited and published by : Division of Chemical Information and Computer Science, The Chemical Society of Japan Produced and listed by : Division of Chemical Information and Computer Science, The Chemical Society of Japan